Clinical features associated with exceptional response on first-line anti-HER2-based therapy for metastatic breast cancer: real-world data from the ESME national cohort.

Some patients with HER2-positive metastatic breast cancer (MBC) achieve prolonged disease control with first-line anti-HER2-based therapy, but associated clinical features remain poorly characterized in real-world populations. We conducted a retrospective study using the Epidemiological Strategy and Medical Economics (ESME) MBC cohort, including 18 French comprehensive cancer centers. Women with HER2-positive MBC who initiated first-line anti-HER2-based therapy between January 2008 and December 2021 and had at least 3 years of follow-up were eligible. Exceptional responders had no documented progression within 3 years. A secondary analysis evaluated factors associated with remaining progression-free at 5 years. Multivariable logistic regression with bootstrap cross-validation was used. Among 4307 eligible patients, 1016 (23.6%) were exceptional responders. Of 765 evaluable at 5 years, 523 (68.4%) remained progression-free. Factors associated with a lower likelihood of exceptional response included hormone receptor-negative (HR-) disease, a disease-free interval of 6-24 months, ≥3 metastatic sites, visceral metastases, and central nervous system involvement. First-line treatment with chemotherapy, trastuzumab, and pertuzumab was associated with exceptional response. Among exceptional responders, HR-disease, grade III tumors and first-line chemotherapy plus trastuzumab and pertuzumab were associated with progression-free at 5-year, whereas visceral metastases were associated with lower odds. Model discrimination was moderate (AUC 0.72 and 0.64, respectively). Nearly one quarter of patients remained progression-free for at least 3 years, and more than two thirds of those evaluable remained progression-free at 5 years. Clinical variables alone had limited predictive value, supporting the need for molecular and immune biomarkers to better identify this subgroup.